1093-P: Incretins and Cardiac Autonomic Function in Youth with Obesity across the Glycemia Spectrum

Abstract

Incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been related to vascular function with variable effects depending on obesity status in adults. The relationship of incretins to vascular function in youth is unclear. We hypothesized that endothelial and cardiac autonomic dysfunction (CAD) are related to lower GLP-1 and GIP in response to glucose ingestion in youth with dysglycemia compared with those with overweight (OW) or normal weight (NW) and normal glucose tolerance (NGT). Adolescents [50 male/52 female; 15.6±1.8 yrs; 24 NW-NGT, 22 OW-NGT, 27 prediabetes and 29 with type 2 diabetes (T2D)] underwent assessment of body composition (DXA scan), 2-hour oral glucose tolerance test (OGTT) with calculation of whole body insulin sensitivity index (WBISI), area under the curve (AUC) of glucose (BG), GLP-1 and GIP. Reactive hyperemia index (RHI), and heart rate variability (HRV), were measured by peripheral arterial tonometry. For HRV, a higher LF/HF (low frequency to high frequency ratio) is indicative of CAD with loss of parasympathetic tone and decreased HRV. The ratios of AUC-GLP-1 and AUC-GIP to AUC-BG were lower in the groups with dysglycemia compared NGT groups (p=0.016 and 0.001, respectively). GLP-1 and GIP were not related to RHI. Fasting and AUC-GLP-1, but not GIP, negatively related to LF/HF (r=-0.37, p=0.002 and r=-0.43, p<0.001 respectively). In a linear regression model with LnLF/HF as the dependent variable, AUC-BG (β=0.31, p=0.04) and AUC-GLP-1 (β=-0.44, p=0.002) contributed to the variance in LnLF/HF independent of %body fat, hs-CRP, WBISI, age, sex, race-ethnicity and Tanner stage (R2= 0.27, p=0.04). Youth with obesity and dysglycemia have impaired incretin response. Glycemia is negatively, whereas GLP-1 is positively associated with HRV after accounting for adiposity, WBIS and inflammation. GLP-1 may be an important determinant of CA function in youth with obesity across the glycemia spectrum. Disclosure H.El ayash: None. F.Bacha: Other Relationship; Takeda Pharmaceutical Co., Ltd., AstraZeneca. Funding U.S. Department of Agriculture-Agricultural Research Service